Polonovski reaction benzodiazepine oxide

The acylation of 1,4-benzodiazepine 4-oxides, e.g. (230), leads to a Polonovski-type rearrangement giving (231) and provides a useful way of functionalizing the 3-position. Treatment of (230) with p-toluenesulfonyl chloride gives the quinoxalone (233) via a Beckmann type of rearrangement (72JHC747, p. 755) and similar rearrangements have been observed in the reactions of 4-hydroxy derivatives with thionyl chloride or phosphorus oxychloride. 

A simple and efficient procedure for the direct oxidation of C-3 of l,4-benzodiazepin-2-ones, applicable to the preparation of the anxiolytic agents oxazepam and lorazepam, has been developed that represents an improvement over the well-established Polonovsky rearrangement of the N-4 oxide <20060PD1192>. Iodine in AcOH at 65 °C catalyzed acetoxylation in a reaction that involved iodination at C-3 followed by a rapid nucleophilic displacement by KOAc. The liberated HI was recycled to iodine by inclusion of a stoichiometric oxidant, with K2S2O8 being the optimal compromise of cost, availability, and efficiency. 

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